Engineering Saccharomyces cerevisiae for production of simvastatin.

ABSTRACT: Simvastatin is a semisynthetic cholesterol-lowering medication and one of the top-selling statins in the world. Currently, industrial production of simvastatin acid (SVA) is a multistep process starting from the natural product lovastatin. For this reason, there is significant interest in direct production of simvastatin from a microbial host. In this study, six heterologous biosynthetic genes were introduced into Saccharomyces cerevisiae and the acyl-donor dimethylbutyryl-S-methyl mercaptopropionate (DMB-SMMP) was added, resulting in initial production of 0.5 mg/L SVA. Switching the yeast strain from JHY686 to BJ5464-NpgA increased total polyketide production to over 60 mg/L and conversion from dihydromonacolin L acid to monacolin J acid (MJA) was increased from 60% to 90% by tuning the c

SUBMITTER: Bond CM 

PROVIDER: S-EPMC6348118 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature